Caspase Inhibition in Islet Transplantation

This study has been completed.

Sponsor:

University of Alberta

ClinicalTrials.gov Identifier:

NCT01653899

First Posted: July 31, 2012

Last Update Posted: July 7, 2016

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This is an Investigator Initiated, Phase I/II study, where Type 1 diabetic participants will receive a 14 day oral treatment of the investigational caspase inhibitor drug IDN-6556 following their first islet transplant. Two pilot studies are proposed to establish the optimal safety and efficacy dose of IDN-6556 (25 mg twice daily (Pilot 1) or a loading dose of 100 mg two hours prior to transplantation, then two 50 mg doses following transplant (Day 0) (Pilot 2). This will be followed by 50 mg three times daily). Participants of both pilot studies will receive islet cell transplants under the University of Alberta's standard-of-care therapy.

Secondary objectives include:

To determine the proportion of subjects treated with IDN-6556 who achieve and maintain insulin independence after the first or subsequent islet transplant.

To obtain preliminary data on the efficacy of IDN-6556 to maintain adequate immunological protection against both allo- and autoimmunity of islet transplant recipients.

Further study details as provided by James Shapiro, University of Alberta:

Primary Outcome Measures:

To assess the safety of the IDN-6556 caspase inhibitor in adult Type 1 diabetic participants receiving their first islet transplant [ Time Frame: 3 years post-initial transplant ]

The primary objective of this protocol is to assess the safety of the IDN-6556 caspase inhibitor in adult Type 1 diabetic participants receiving their first islet transplant. A tracking log will document adverse events and unexpected complications associated with IDN-6556 using a grading classification as per protocol.

Secondary Outcome Measures:

1. To determine the proportion of subjects treated with IDN-6556 who achieve and maintain insulin independence after the first or subsequent islet transplant. [ Time Frame: 3 years post-initial transplant ]

The proportion of study participants achieving and maintaining insulin independence (c-peptide, HbA1c level) with good glycemic control (blood sugar measurement) at Day 90 and 1, 2, 3 years post-initial islet transplant.

2. To obtain preliminary data on the efficacy of IDN-6556 to maintain adequate immunological protection against both allo- and autoimmunity of islet transplant recipients. [ Time Frame: 3 years post-initial transplant ]

Immune monitoring for HLA and panel reactive antibody will be performed using serum samples

14 day oral treatment of the investigational caspase inhibitor drug IDN-6556 following first islet transplant at 50mg twice daily.

Other Name: Emricasan

Eligibility

Information from the National Library of Medicine

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Ages Eligible for Study:

18 Years to 68 Years (Adult, Senior)

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

No

Criteria

Inclusion Criteria:

To be eligible the participant must have had T1DM for more than 5 years, complicated by at least 1 of the following situations that persist despite intensive insulin management efforts:

Active alcohol or substance abuse, to include cigarette smoking (must be abstinent for 6 months prior to transplant).

Psychiatric disorder making the subject not a suitable candidate for transplantation, (e.g., schizophrenia, bipolar disorder, or major depression that is unstable or uncontrolled on current medication).

History of non-adherence to prescribed regimens.

Active infection including Hepatitis C, Hepatitis B, HIV, TB (subjects with a positive PPD performed within one year of enrollment, and no history of adequate chemoprophylaxis).

Any history of or current malignancies except squamous or basal skin cancer.

Baseline screening liver function tests outside of normal range, with the exception of uncomplicated Gilbert's Syndrome. An initial LFT panel with any values > 1.5 times the upper limit of normal (ULN) will exclude a patient without a re-test; a re test for any values between ULN and 1.5 times ULN should be made, and if the values remain elevated above normal limits, the patient will be excluded.